{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Petrucci G"],"funding":["Cancer Research UK"],"pubmed_abstract":["Low-dose aspirin is currently recommended for patients with polycythemia vera (PV), a myeloproliferative neoplasm with increased risk of arterial and venous thromboses. Based on aspirin pharmacodynamics in essential thrombocythemia, a twice-daily regimen is recommended for patients with PV deemed at particularly high thrombotic risk. We investigated the effects of low-dose aspirin on platelet cyclooxygenase activity and in vivo platelet activation in 49 patients with PV, as assessed by serum thromboxane (TX) B<sub>2</sub> and urinary TXA<sub>2</sub> /TXB<sub>2</sub> metabolite (TXM) measurements, respectively. A previously described pharmacokinetic-pharmacodynamic in silico model was used to simulate the degree of platelet TXA<sub>2</sub> inhibition by once-daily (q.d.) and twice-daily (b.i.d.) aspirin, and to predict the effect of missing an aspirin dose during q.d. and b.i.d. regimens. Serum TXB<sub>2</sub> averaged 8.2 (1.6-54.7) ng/ml and significantly correlated with the platelet count (γ = 0.39) and urinary TXM (γ = 0.52) in multivariable analysis. One-third of aspirin-treated patients with PV displayed less-than-maximal platelet TXB<sub>2</sub> inhibition, and were characterized by significantly higher platelet counts and platelet-count corrected serum TXB<sub>2</sub> than those with adequate inhibition. Eight patients with PV were sampled again after 12 ± 4 months, and had reproducible serum TXB<sub>2</sub> and urinary TXM values. The in silico model predicted complete inhibition of platelet-derived TXB<sub>2</sub> by b.i.d. aspirin, a prediction verified in a patient with PV with the highest TXB<sub>2</sub> value while on aspirin q.d. and treated short-term with a b.i.d. regimen. In conclusion, one in three patients with PV on low-dose aspirin display less-than-maximal inhibition of platelet TXA<sub>2</sub> production. Serum TXB<sub>2</sub> measurement can be a valuable option to guide precision dosing of antiplatelet therapy in patients with PV."],"journal":["Clinical and translational science"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9747129"],"repository":["biostudies-literature"],"pubmed_title":["Platelet thromboxane inhibition by low-dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation."],"pmcid":["PMC9747129"],"pubmed_authors":["Ranalli P","Petrucci G","Dragani A","Tremoli E","Cavalca V","Giaretta A","Porro B","Patrono C","Rocca B","Hatem D","Habib A"],"additional_accession":[]},"is_claimable":false,"name":"Platelet thromboxane inhibition by low-dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation.","description":"Low-dose aspirin is currently recommended for patients with polycythemia vera (PV), a myeloproliferative neoplasm with increased risk of arterial and venous thromboses. Based on aspirin pharmacodynamics in essential thrombocythemia, a twice-daily regimen is recommended for patients with PV deemed at particularly high thrombotic risk. We investigated the effects of low-dose aspirin on platelet cyclooxygenase activity and in vivo platelet activation in 49 patients with PV, as assessed by serum thromboxane (TX) B<sub>2</sub> and urinary TXA<sub>2</sub> /TXB<sub>2</sub> metabolite (TXM) measurements, respectively. A previously described pharmacokinetic-pharmacodynamic in silico model was used to simulate the degree of platelet TXA<sub>2</sub> inhibition by once-daily (q.d.) and twice-daily (b.i.d.) aspirin, and to predict the effect of missing an aspirin dose during q.d. and b.i.d. regimens. Serum TXB<sub>2</sub> averaged 8.2 (1.6-54.7) ng/ml and significantly correlated with the platelet count (γ = 0.39) and urinary TXM (γ = 0.52) in multivariable analysis. One-third of aspirin-treated patients with PV displayed less-than-maximal platelet TXB<sub>2</sub> inhibition, and were characterized by significantly higher platelet counts and platelet-count corrected serum TXB<sub>2</sub> than those with adequate inhibition. Eight patients with PV were sampled again after 12 ± 4 months, and had reproducible serum TXB<sub>2</sub> and urinary TXM values. The in silico model predicted complete inhibition of platelet-derived TXB<sub>2</sub> by b.i.d. aspirin, a prediction verified in a patient with PV with the highest TXB<sub>2</sub> value while on aspirin q.d. and treated short-term with a b.i.d. regimen. In conclusion, one in three patients with PV on low-dose aspirin display less-than-maximal inhibition of platelet TXA<sub>2</sub> production. Serum TXB<sub>2</sub> measurement can be a valuable option to guide precision dosing of antiplatelet therapy in patients with PV.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-04-04T19:11:15.215Z","creation":"2025-04-04T19:11:15.215Z"},"accession":"S-EPMC9747129","cross_references":{"pubmed":["36200184"],"doi":["10.1111/cts.13415"]}}